title: Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide.
abstract: Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury.
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Mo
authors.forename: Connie F
authors.initials: CF
authors.lastname: Schlueter
authors.forename: Gary W
authors.initials: GW
authors.lastname: Hoyle
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D002713:Chlorine / Q000633:toxicity*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D000068656:Mometasone Furoate; D020556:Neutrophil Infiltration / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011244:Pregnadienediols / Q000008:administration & dosage / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D002713:Chlorine; D019819:Budesonide
keywords: Acute lung injury; Corticosteroids; Pneumonitis; Pulmonary edema